Bleeding Hand Mass in an Older Man

The Diagnosis: Epithelioid Angiosarcoma

Histopathology showed a large soft-tissue neoplasm with extensive hemorrhage (Figure 1). The epithelioid angiosarcoma (EA) consisted mostly of irregular slit-shaped vessels lined by sheets of atypical endothelial cells (Figure 2). At higher-power magnification, the cellular atypia was prominent and diffuse (Figure 3). Immunostaining of the tumor cells showed positive uptake for CD31, confirming vascular origin (Figure 4). Other vascular markers, including CD34 and factor VIII, as well as nuclear positivity for the erythroblast transformation-specific transcription factor gene, ERG, can be demonstrated by EA. Irregular, smooth muscle actin-positive spindle cells are distributed around some of the vessels. The human herpesvirus 8 stain is negative.

Figure 1. A large soft-tissue neoplasm with extensive hemorrhage (H&E, original magnification ×5)

Figure 2. The tumor consisted of a sheet of cells and focal areas of irregular slit-shaped vessel formation (H&E, original magnification ×10).

Figure 3. Cells were atypical and polygonal with eccentric nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, consistent with epithelioid cells (H&E, original magnification ×30).

Figure 4. Immunostaining of the epithelioid cells was focally positive for CD31 (original magnification ×5).

Compared to classic angiosarcomas, EAs have a predilection for the extremities rather than the head and scalp. Histopathologically, the cells are epithelioid and are strongly positive for vimentin and CD31, in addition to factor VIII, friend leukemia integration 1 transcription factor, and CD34.^1,2 In contrast, epithelioid sarcomas more typically are seen in younger adults and less likely to be CD31 positive.³ An epithelioid hemangioendothelioma is more focal in cellular atypia and forms small nests and trabeculae rather than sheets of atypical cells. Melanoma cells stain positive for human melanoma black 45, Melan-A, and S-100 but not for CD31.³ Glomangiosarcomas typically stain positive for smooth muscle actin and muscle-specific actin.⁴

Epithelioid angiosarcomas are rare and aggressive malignancies of endothelial origin.³ They are more prevalent in men and have a peak incidence in the seventh decade of life. They most commonly occur in the deep soft tissues of the extremities but have been reported to form in a variety of primary sites, including the skin, bones, thyroid, and adrenal glands.³

Tumors tend to be highly aggressive and demonstrate early nodal and solid organ metastases.³ Our case demonstrated the aggressive nature of this high-grade malignancy by showing neoplastic invasion through a vascular wall. Within 2 to 3 years of diagnosis, 50% of patients die of the disease, and the 5-year survival rate is estimated to be 12% to 20%.^3,5 The etiology remains unknown, but EA has been linked to prior exposure to toxic chemicals, irradiation, or Thorotrast contrast media, and it may arise in the setting of arteriovenous fistulae and chronic lymphedema.⁶

Although radiation therapy often is utilized, surgery is the primary treatment modality.⁵ Even with wide excision, local recurrence is common. Tumor size is one of the most important prognostic features, with a worse prognosis for tumors larger than 5 cm. Evidence suggests that paclitaxel-based chemotherapeutic regimens may improve survival, and a combination of paclitaxel and sorafenib has been reported to induce remission in metastatic angiosarcoma of parietal EA.⁵ Currently, no standardized treatment regimen for this condition exists.

Acknowledgment
The authors thank Amanda Marsch, MD (Chicago, Illinois), for obtaining outside pathology consultation.